Polymorphonuclear leukocytes (PMN) are the infantry of the cellular host defense system. As such, they constitute the first line of defense against bacterial initial periodontal disease (PD). To prevent PD PMNs must be able to chemotax, phagocytose, degranulate and kill bacteria. Bacteria can avoid the PMNs by disabling or killing them. Evidence indicates that the periodontal pathogen, capnocytophaga Type 4, can disable PMN function. Circumstantial evidence suggests that the disabling mechanism is similar to the mechanism of action of the drug cytochalasin. In this application we will examine this hypothesis. Namely, that factors derived from capnocytophaga sonicates directly or indirectly disable PMN function by disrupting their cytoskeleton. The experiments proposed in this application will utilize intact human PMNs. The PMNs will be examined in the transmission EM and the organization of the actin cytokelton examined. Normal PMNs, PMNs treated with cytochalasin and PMNs treated with sonicates from capnocytophaga will be compared. Three items will be of interest: (1) the length of the actin filaments; (2) the number of ends of the actin filaments; and (3) the density of the actin filament matrix in a given area of the PMN. The drug cytochalasin and the sonicate will be applied to both whole and extracted cells. This will allow us to determine whether the affect is upon the cell membrane (and indirectly affects the cytoskeleton) or directly upon the cytoskeleton (which is the case for cytochaalasin). If, as we suspect, the capnocytophaga toxin affects the cytoskeleton, it will provide a first step in unraveling one pathogenetic mechanism for periodontal disease.